Fluid challenge during anesthesia: a systematic review and meta-analysis Antonio Messina, PhD1; Corrado Pelaia, MD2; Andrea Bruni, MD2; Eugenio Garofalo, MD2; Eleonora Bonicolini, MD3; Federico Longhini, MD4; Erica Dellara, MD4; Laura Saderi, BSc5; Stefano Romagnoli, MD3; Giovanni Sotgiu, MD, FERS5; Maurizio Cecconi MD, FRCA, FICM1; Paolo Navalesi, MD, FERS2. 1IRCCS Humanitas, Humanitas University, Milano, Italy, 2Anesthesia and Intensive Care, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy, 3Department of Anesthesia and Critical Care, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy; 4Anesthesia and Intensive Care Medicine, Sant’Andrea Hospital, Vercelli, Italy, 5Clinical Epidemiology and Medical Statistics Unit, Dept of Biomedical Sciences, University of Sassari, Research, Medical Education and Professional Development Unit, AOU Sassari, Sassari, Italy. Online Supplement Research Strategy The research was performed using Medline and EMBASE databases. The following terms were included: “fluid challenge” OR “fluid responsiveness” OR “fluid therapy” OR “fluid optimization” AND “stroke volume variation” OR “pulse pressure variation” OR “dynamic indices OR indexes” AND “intraoperative fluid optimization”, OR “surgery” OR “directed therapy” OR “goal-directed therapy” OR “goal oriented” OR “goal targeted”. The research was limited by language (English), age of participants (adults) and availability of full text article (if only the abstract of the article has been published it was not included in the review). The database’s filters were used in order to follow the research strategy. SUPPLEMENTARY TABLES Supplement Table 1. Comparisons of the characteristics of the population in GDT studies Variables Treatments Controls p-value Total group, n 1775 1806 Median (IQR) age, years 66 (60-70) 67 (63-72) 0.51 Median (IQR) ASA I, % 2.1 (0-12.8) 2.7 (0-11.2) 0.99 Mean (SD) ASA II, % 49.8 (29.1) 48.8 (28.9) 0.92 Mean (SD) ASA III, % 44.5 (32.6) 43.5 (32.9) 0.93 Median (IQR) ASA IV, % 0 (0-2.8) 0 (0-2.5) 0.52 Median (IQR) duration of surgery, minutes 167 (147 - 248) 174 (148 -257) 0.84 Median (IQR) total amount of fluid infused, ml 2500 (1056-5.000) 2758 (1385-4494) 0.91 Mean (SD) colloids, ml 1157 (529) 698 (456) 0.001 Median (IQR) crystalloids, ml 1422 (960 - 2489) 2.000 (1129-2888) 0.29 Median (IQR) estimated blood loss, ml 500 (300-980) 500 (350-900) 0.98 Abbreviations: GDT, Goal-Directed Therapy; IQR, interquartile; SD, standard deviation; ASA, American Society of Anaesthesiologists score. Supplemental Figure 1. Forest and funnel plots of pooled value of sensitivity (left panel) and specificity (right panel) of the 10 studies included in the metanalysis of pulse pressure variation reliability in predicting fluid responsiveness. PPV, pulse pressure variation. Supplemental Figure 2. Forest and funnel plots of pooled value of sensitivity (left panel) and specificity (right panel) of the 16 studies included in the metanalysis of stroke volume variation reliability in predicting fluid responsiveness. SVV, stroke volume variation. Supplemental Figure 3. Estimated ROC curves with upper and lower limits of the 95% confidence intervals of baseline pulse pressure variation [left panel, 10 studies, AUC = 0.86 (95%CI, 0.80- 0.92)] and stroke volume variation [right panel, 16 studies, AUC = 0.87 (95%CI, 0.81-0.93)] reporting the ability to discriminate between responders and non-responders after FC administration (software MetaDiSC®, version 1.4, see text for more data details). PPV, pulse pressure variation; SVV, stroke volume variation; AUC, area under the curve. .